Advances in microelectronics and MEMS technologies paved the way for sensing devices at the scale of a millimeter or less which allows the devices to be implanted for direct interaction with organ systems using simpli?ed delivery vi a catheter or hypodermic needle, but technologies for powering or communicating with them remain bulky and inef?cient. This severely limits its use beyond home monitoring. The long-term goal of this proposal is to develop a compact and patient friendly monitoring system that can assimilate seamlessly into patients' daily lives for on-demand and real-time disease management from anywhere at any time. The proposed method will allow the use of a compact and ?exible source structure to power and communicate with deeply implanted, minuscule sensors. This is made possible by the recent development of mid?eld wireless powering approaches in the PI's laboratory, a wireless interface that exploits the wave-tissue interactions in the electromagnetic mid?eld regime, achieves orders of magnitude better performance than conventional wireless systems that conceptually ignore the tissue environment. Following on this exciting development, we will devise a combined power harvesting structure and communication antenna that is about 5 cm in the largest dimension and fabricated on a ?exible substrate for an operational range of 5 cm to 15 cm deep in a complex tissue environment. The ?eld patterns from this external structure can be electronically changed. We will develop low-latency algorithms and low-power transceivers to locate the sensor without the need of any intervention from the patient. Integrating the wireless interface with a sensor interface on a single chip, we seek to demonstrate a highly miniaturized sensing system. With the support from St. Jude Medical, we will test and validate the proposed system for pulmonary artery pressure monitoring. The success of this demonstration will open the door to a new realm of possibilities for real-time, chronic disease management. In addition to sense and process physiological states, the proposed system will eventually incorporate stimulation and actuation capabilities to respond to disease states, enabling closed-loop disease treatment.